On November 14, 2023 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, reported financial results for the third quarter ended September 30, 2023, and recent business progress (Press release, TransCode Therapeutics, NOV 14, 2023, View Source [SID1234637641]).

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"In the third quarter of 2023, we successfully completed a follow-on public offering in a very difficult biotech market as we continue our clinical study with our lead therapeutic candidate, an RNA targeted therapeutic candidate for treating metastatic disease," said Michael Dudley, co-founder, president and Chief Executive Officer of TransCode. "We were excited to dose our first patient in our Phase 0 clinical trial with TTX-MC138 in cancer patients with advanced solid tumors for which further enrollment is underway.

TransCode co-founder and Chief Technology Officer, Dr. Zdravka Medarova, commented, "We also announced encouraging preclinical data in glioblastoma multiforme (GBM) with our lead candidate. In addition, we published results of a preclinical study showing that inhibition of microRNA-10b, the therapeutic target of TTX-MC138, in breast cancer cells impaired the capacity of cancer stem cells to create new tumors and become metastatic. We believe these findings are important because cancer stem cells have long been known to play a critical role in cancer initiation, metastasis, recurrence, and resistance to therapy. Therefore, we believe that inhibiting the tumor-creating capacity of these cells using TTX-MC138 has the potential to improve outcomes in patients with breast cancer that is recurrent and resistant to treatment."

Recent Business Highlights

· In July, the company announced the results of a pre-clinical study of its lead therapeutic candidate, TTX-MC138, in non-human primates, effectively engaging its target and showing favorable pharmacokinetics and tissue distribution. In the study, non-human primates (n = 4) were injected with a microdose of radiolabeled TTX-MC138 and imaged by positron emission tomography-magnetic resonance imaging (PET-MRI) to determine the pharmacokinetics and tissue distribution of the therapeutic candidate. In addition, the pharmacodynamic activity of radiolabeled TTX-MC138 following a microdose injection was determined by measuring inhibition of its target, miRNA-10b, using qRT-PCR. TTX-MC138 demonstrated a long circulation half-life and tissue distribution consistent with hepatic clearance. Importantly, even at a microdose, the therapeutic candidate showed lasting activity and significantly inhibited miRNA-10b, known to be a driver of metastatic progression in a number of cancers.

· In August, the company dosed the first patient in its First-in-Human Phase 0 clinical study. The Phase 0 trial is an open-label, single-center, microdose study intended to demonstrate delivery of the radiolabeled version of TTX-MC138 to radiographically-confirmed metastases in subjects with advanced solid tumors. Preliminary data showed that radioactivity consistent with accumulation of TTX-MC138 was detected by noninvasive imaging in the regions of the metastatic lesions previously identified by fluorodeoxyglucose (FDG)/positron emission tomography (PET) (FDG/PET). In addition, radiolabeled TTX-MC138 had pharmacokinetic behavior consistent with that expected based on non-clinical IND-enabling studies. The patient tolerated the dosing with no reported adverse reactions. Metabolite analysis indicated circulation of intact radiolabeled TTX-MC138 for more than 20 hours, equivalent to that predicted by Drug Metabolism and Pharmacokinetics (DMPK) modelling, and that the drug candidate analyzed in the blood was identical to that of the manufactured drug candidate, demonstrating in vivo stability. Complete analysis of data from this first patient is in process and will be included in the final report for all patients enrolled in the study.

· In September, the company announced the results of a pre-clinical study of TTX-MC138 in murine models bearing human glioblastoma multiforme (GBM) tumors. In this study, the therapeutic candidate was delivered to brain tumors where it effectively engaged its target. In the study reported by TransCode, mice implanted with tumors derived from human GBM patients were treated with TTX-MC138 and imaged by magnetic resonance imaging (MRI) to determine delivery of the therapeutic candidate to the tumors. In addition, the pharmacodynamic activity of TTX-MC138 was determined by measuring inhibition of miRNA-10b using qRT-PCR. TTX-MC138 was injected intravenously and accumulated efficiently in the tumors. Importantly, the therapeutic candidate showed lasting activity and significantly inhibited miRNA-10b, known to be a driver of tumor progression in glioblastoma.

· Also, in September, the company closed an underwritten public offering of an aggregate of 16,863,000 shares of its common stock (or pre-funded warrants in lieu thereof), including the partial exercise of the underwriter’s over-allotment option. Each share of common stock (or pre-funded warrant) was sold at a public offering price of $0.51 per share (inclusive of the pre-funded warrant exercise price of $0.01 per share). All of the shares and pre-funded warrants in the offering were sold by the company. Gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses, were approximately $8.5 million.

Planned Milestones

TransCode’s goals to continue to advance its portfolio include:

· TTX-MC138

o Enroll additional patients in First-in-Human Phase 0 clinical trial intended to demonstrate quantifiable evidence of delivery of radiolabeled TTX-MC138 to metastatic lesions in advanced solid tumors; measure pharmacokinetics and biodistribution in vital organs and other tissues; potentially inform therapeutic dose levels for future trials based on Phase 0 microdose results; and potentially validate delivery for the TTX pipeline more broadly, which could open-up additional relevant RNA targets that have been previously undruggable due to challenges with RNA delivery.

○ Submission to FDA of an Investigational New Drug (IND) application for a Phase I clinical trial with TTX-MC138.

· Publication of preclinical in vivo studies supporting therapeutic candidates, TTX-RIGA and TTX-siPDL1, as well as TTX-MC138 in pancreatic adenocarcinoma.

· Continuation of discussions with potential strategic partners regarding partnerships in multiple therapeutic areas including CRISPR and intracellular delivery of proteins using TransCode’s TTX delivery platform.

· Filing for orphan drug designation for TTX-MC138 in additional tumor indications.

Third Quarter 2023 Financial Highlights

· Cash was approximately $7.5 million at September 30, 2023, compared to approximately $5.0 million at December 31, 2022.

· Research and development expense was approximately $3.3 million in the third quarter of 2023, compared to approximately $3.0 million in the third quarter of 2022.

· General and administrative expense was approximately $2.0 million in the third quarter of 2023, compared to approximately $1.9 million in the third quarter of 2022.

· Operating loss for the three months ended September 30, 2023, was approximately $5.3 million, compared to an operating loss of approximately $4.3 million in the prior year period.

Financial Guidance

TransCode expects that its cash of approximately $7.5 million as of September 30, 2023, is sufficient to fund planned operations into January 2024 but not for a full 12 months from the date of its financial statements.

On November 14, 2023 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology, obesity and non-alcoholic steatohepatitis (NASH), reported financial results for the quarter ended September 30, 2023 and provided corporate updates (Press release, Terns Pharmaceuticals, NOV 14, 2023, View Source [SID1234637640]).

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"Throughout the third quarter and in recent weeks, we made meaningful progress across all three of our clinical development programs, opening U.S. Investigational New Drug (IND) applications, both for our allosteric BCR-ABL inhibitor TERN-701 for chronic myeloid leukemia (CML) and our lead small molecule oral GLP-1 agonist TERN-601 for obesity, and releasing Phase 2 data for our thyroid hormone receptor β agonist TERN-501 from the DUET study in NASH patients. We are now preparing for a data-rich 2024, with expected proof of concept readouts from our clinical trials in CML and obesity," stated Erin Quirk, MD, president and head of research and development at Terns. "The advances we are making, which are supported by strong clinical and scientific data, give us even greater confidence in our approach to bring better chemistry to the development of small-molecule candidates with clinically validated mechanisms to address oncologic and metabolic diseases with large unmet medical needs."

"We are excited to have dosed the first participant in our first-in-human trial of TERN-601 to treat obesity as preclinical data suggest it has potential for broad metabolic benefits in obesity, oral once-daily dosing, and suitability for combination therapy. We are also looking forward to dosing the first participants in our Phase 1 trial of TERN-701 as a treatment for CML while leveraging insights from our partner’s ongoing Phase 1 trial in China to support a starting dose that appears safe and clinically active based on emerging early clinical data," added Dr. Quirk.

Recent Pipeline Developments and Anticipated Milestones

TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for CML
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In October, Terns announced the Investigational New Drug (IND) clearance from the U.S. FDA and design of the CARDINAL Phase 1 clinical trial of TERN-701 for the treatment of CML
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CARDINAL is a global, multicenter, open-label, two-part Phase 1 clinical trial to evaluate the safety, pharmacokinetics (PK), and efficacy of TERN-701 in participants with previously treated CML
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The dose escalation portion (Part 1) of the trial will evaluate once-daily TERN-701 monotherapy in approximately 24-36 adults living with CML to be enrolled in up to five dose cohorts; screening for Part 1 is anticipated to begin in December 2023

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Primary endpoints of the CARDINAL dose escalation portion include incidence of dose limiting toxicities (DLTs) during the first treatment cycle and additional measures of safety and tolerability
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Secondary endpoints include PK and efficacy assessments, such as hematologic and molecular responses as measured by the change from baseline in BCR-ABL transcript levels
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The starting dose is 160 mg QD (once-daily), with the option to explore a lower dose of 80 mg QD
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The dose expansion portion (Part 2) of the CARDINAL trial will initiate after dose escalation data are available and will enroll approximately 40 patients, randomized to once-daily treatment with one of two doses of TERN-701 to be selected based on data from Part 1
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The primary endpoint of the CARDINAL dose expansion portion is efficacy, measured by hematologic and molecular responses. Secondary endpoints include safety, tolerability and PK
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The CARDINAL trial plans to enroll at sites in the United States, Europe and other global territories
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Global site identification and trial start-up activities are ongoing, with interim top-line readouts from initial cohorts expected in the second half of 2024

TERN-601: Oral, small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist for obesity

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Earlier this month, Terns announced that the first participant was dosed in the Phase 1 first-in-human clinical trial of TERN-601 for obesity
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The Phase 1 trial is a randomized, double-blind, placebo-controlled single and multiple-ascending dose (SAD and MAD) trial to assess the safety, tolerability, PK and pharmacodynamics (PD) of TERN-601 in healthy adults with obesity or who are overweight
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Part 1 (SAD) is a SAD study that will evaluate up to six once-daily TERN-601 dose levels in approximately 40 healthy participants
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The starting TERN-601 dose is 30 mg, with subsequent dose levels based on review of emerging safety and PK data from prior cohorts
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Part 2 (MAD) of the trial will enroll approximately 72 obese and overweight healthy participants and will include cohorts incorporating titration of TERN-601 administered for 28-days at doses to be selected based on data from Part 1
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Top-line, 28-day proof of concept weight loss data from the Phase 1 trial is expected in the second half of 2024

TERN-501: Oral, thyroid hormone receptor-β (THR-β) agonist for NASH

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Phase 2a DUET trial data evaluating TERN-501 for the treatment of NASH was featured in an oral late-breaking presentation at The Liver Meeting 2023:
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The oral presentation titled, "Topline results from a 12-week Phase 2a Trial (DUET) evaluating TERN-501, a highly selective thyroid hormone receptor (THR) β agonist, either as monotherapy or in combination with TERN-101, a nonsteroidal farnesoid X receptor (FXR) agonist, demonstrated significant reductions in MR-based liver fat content and fibroinflammation in patients with presumed NASH," was delivered by Mazen Noureddin, MD, MHSc, Professor of Medicine, Academic Institute at Houston Methodist, Director of Houston Research Institute
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Terns reported positive top-line data from the Phase 2a DUET trial of TERN-501 for the treatment of NASH in August
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TERN-501 met all primary and secondary endpoints
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TERN-501 demonstrated dose dependent MRI-PDFF reductions at Week 12 as a once-daily, low dose, and combinable oral therapy
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TERN-501 (6 mg) showed statistically significant mean relative liver fat content reduction of 45% as assessed by MRI-PDFF with 64% of patients achieving >30% PDFF reduction
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All TERN-501 doses were well-tolerated with no gastrointestinal and no cardiovascular safety signals

Corporate Updates

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In August 2023, Terns announced the departure of Senthil Sundaram, the Company’s former chief executive officer, for health reasons. Terns is conducting an ongoing search for a permanent chief executive officer. In the interim, Dr. Quirk continues to assume day-to-day leadership of the Company and serve as principal executive officer. In addition, the Board has engaged board director, Jill M. Quigley, JD as senior advisor and strategy officer on an interim basis until a permanent chief executive officer is appointed.

Third Quarter 2023 Financial Results

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Cash Position: As of September 30, 2023, cash, cash equivalents and marketable securities were $266.6 million, as compared with $283.1 million as of December 31, 2022. Based on its current operating plan, Terns expects these funds will be sufficient to support its planned operating expenses into 2026.
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Research and Development (R&D) Expenses: R&D expenses were $14.8 million for the quarter ended September 30, 2023, as compared with $12.2 million for the quarter ended September 30, 2022.
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General and Administrative (G&A) Expenses: G&A expenses were $18.4 million for the quarter ended September 30, 2023, as compared with $5.1 million for the quarter ended September 30, 2022.
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Net Loss: Net loss was $29.8 million for the quarter ended September 30, 2023, as compared with $16.8 million for the quarter ended September 30, 2022.

On November 14, 2023 Sigyn Therapeutics, Inc. ("Sigyn" or the "Company") (OTCQB: SIGY), a development-stage medical technology company, reported its financial results for the third quarter ended September 30, 2023 (Press release, Sigyn Therapeutics, NOV 14, 2023, View Source [SID1234637639]).

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During the quarter, the Company continued its plan to initiate first-in-human studies of Sigyn TherapyTM and further advanced its endeavors to develop pipeline technologies to enhance the performance of cancer therapies. The initial treatment indication of Sigyn TherapyTM is being directed toward end-stage renal disease (ESRD) patients with endotoxemia, a condition that is highly prevalent and associated with increased mortality in the ESRD population. The Company has identified three clinical site locations and is working with principal investigators to finalize the study protocol. Once finalized, the Company intends to submit an Investigational Device Exemption (IDE) to The U.S. Food and Drug Administration (FDA) requesting permission to enroll up to 15 ESRD subjects with the primary objective to demonstrate the safety of Sigyn TherapyTM.

Summary of Third Quarter 2023 Financial Results

For the quarter ended September 30, 2023, the Company had a loss from operations of approximately $642,814, compared to an operating loss of approximately $533,647 for the comparable period of 2022. The Company’s net loss for the 2023 third quarter was approximately $905,726 or approximately $0.02 per share, compared to a net loss of approximately $726,509, or approximately $0.02 per share, for the comparable period in 2022.

For complete financial results, please see Sigyn Therapeutics’ filings at www.sec.gov, and on the Company’s website at www.SigynTherapeutics.com under "Financial Info" in the Investors section.

On November 14, 2023 RenovoRx, Inc. ("RenovoRx" or the "Company") (Nasdaq: RNXT), a clinical-stage biopharmaceutical company developing targeted combination therapies, reported financial results for the third quarter ended September 30, 2023 (Press release, Renovorx, NOV 14, 2023, View Source [SID1234637638]).

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"We remain focused on our core mission to improve the lives of patients diagnosed with difficult-to-treat cancers by delivering novel targeted combination therapies that have the potential to alter the current paradigm of oncology care," said Shaun Bagai, CEO of RenovoRx. "We are encouraged by the progress in our pivotal Phase III TIGeR-PaC study, and the recent completed interim analysis, along with our partnership with Imugene as we explore pipeline expansion opportunities using our TAMP therapy platform."

Key Business Highlights:

● Continued to advance Phase III TIGeR-PaC clinical trial for the treatment of LAPC. The first of two interim analyses was completed in March 2023, and the Data Monitoring Committee recommended a continuation of the study. The study is prespecified to provide a primary endpoint of a 6-month OS benefit and secondary endpoints including reduced adverse events versus standard of care. Additionally, Dr. Michael J. Pishvaian, Johns Hopkins Medicine and Principal Investigator of TIGeR-PaC, presented at the Global Summit on Gastrointestinal Malignancies in Bermuda. The presentation, "Increasing Local Gemcitabine Delivery Using TAMP in the Chemotherapy Advances in Pancreatic Cancer," highlighted the proprietary TAMP therapy platform and its design to ensure precise delivery for targeted treatment of cancer, and its potential for increased safety, tolerance, and improved efficacy.
● Ripal Gandhi, FSIR, FSVM, investigator in the TIGeR-PaC study, presented, "Advances in Pancreatic Cancer: Trans-arterial Therapy on the Horizon," at the Symposium on Clinical Interventional Oncology (CIO) on September 22-24, 2023, in Orlando, Florida. Dr. Gandhi highlighted the TAMP therapy platform as a potential targeted treatment option for patients diagnosed with locally advanced pancreatic cancer versus the standard of care. Dr. Gandhi is a member of the Miami Cancer Institute and Miami Cardiac and Vascular Institute physician team, a Clinical Professor at Florida International University Herbert Wertheim College of Medicine and Associate Professor at USF School of Medicine.
● Collaboration with Imugene Ltd (ASX: IMU) further validates the TAMP platform and will expand use of RenovoRx’s delivery platform beyond chemotherapy to immunotherapy.

Financial Highlights for Third Quarter ended September 30, 2023:

● Cash Position: Cash and cash equivalents as of September 30, 2023, were $3.2 million.
● R&D Expenses: Research and development expenses were $1.6 million for the quarter ended September 30, 2023, compared to $0.8 million for the quarter ended September 30, 2022. The increase was primarily due to our ongoing Phase III clinical trial cost of $0.4 million, an increase in employee and related benefits costs of $0.3 million and general and administrative allocated costs of $0.2 million. This increase was partially offset by a decrease in costs associated with a secondary manufacturer of $0.1 million.
● G&A Expenses: General and administrative expenses were $1.3 million for the third quarter ended September 30, 2023, flat compared to the same period last year. Employee and related benefits costs increased $0.3 million compared to the same quarter last year. This increase was offset by a decrease in directors’ and officers’ insurance expenses of $0.1 million, including allocation of general and administrative expenses to research and development of $0.2 million.
● Net Loss: Net loss was $1.4 million for the quarter ended September 30, 2023, compared to net loss of $2.1 million for the quarter ended September 30, 2022. The decrease is primarily due to an increase in operating expenses of $0.8 million, offset by $1.5 million reported gain on the fair value of common warrants issued under our Registered Direct Offering in April 2023.
● Shares Outstanding: Shares of common stock outstanding, as of September 30, 2023, were 10,693,080.

On November 14, 2023 QSAM Biosciences Inc. (OTCQB: QSAM), a company developing therapeutic radiopharmaceuticals for the treatment of primary and secondary bone cancer and related conditions, reported that it has signed a non-binding term sheet (the "Term Sheet") with Telix Pharmaceuticals (US) Inc., a subsidiary of Telix Pharmaceuticals Limited (ASX: TLX) (collectively, "Telix") providing material terms for the acquisition of the Company by Telix by means of a merger (the "Acquisition"). Upon signing of the Term Sheet, Telix has agreed to pay the Company a US$2 million Pre-Closing Collaboration and Option Fee (the "Collaboration Fee") to advance the Company’s development efforts based on mutually agreed goals and to provide sixty days of exclusivity pending completion of diligence and execution of a definitive acquisition agreement (Press release, QSAM Biosciences, NOV 14, 2023, View Source [SID1234637637]).

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Among the material terms still subject to diligence and definitive agreements, upon closing of the Acquisition, Telix is expected to pay a total of US$33.1 million in Telix stock and up to US$90 million in contingent clinical and commercial milestone payments through a Contingent Value Rights ("CVR") structure. If the Acquisition does not close, the Collaboration Fee will be converted to Company common stock at a price of 6.70 per share.

Dr. C. Richard Piazza, QSAM’s Executive Chairman and co-Founder, stated, "We are thrilled to commence working with Telix by virtue of the Collaboration Fee to advance our technology and pursue a definitive agreement leading to the acquisition of QSAM by Telix. Over the last few months, we have gotten to know Telix’s unique strengths and resources in the radiopharmaceutical space and believe a business combination with them would provide the greatest chances of success for CycloSam and for our shareholders. We will be working diligently to try to get this transaction completed in the first quarter of 2024."

Dr. Christian Behrenbruch, Managing Director and Group CEO of Telix, continued, "We are pleased to announce our intention to acquire QSAM. This acquisition will bring a validated therapeutic candidate with the potential to accelerate development under the Orphan Drug and Rare Pediatric Disease designations, and a highly experienced team that has completed numerous FDA approvals. With CycloSam we plan to leverage Telix’s extensive experience and success in distributing short-life radiopharmaceuticals using a cold kit product from a nuclear pharmacy. Given these factors, we see a strong pathway to commercialization."

The Acquisition is subject to the satisfactory completion of diligence by both parties, execution of definitive agreements, and approval by the QSAM shareholders, among other conditions.